The Use of Low Dose Heparin (LDH) for DVT/PE Prophylaxis

I.   Statement of the Problem

The fact that DVT and PE occur following trauma is incontrovertible. The optimal mode of prophylaxis has yet to be determined. Low dose heparin (LDH) given in doses of 5000 units subcutaneously two or three times daily represents one pharmacologic treatment modality used for prophylaxis against DVT/PE.

To date, a robust analysis of the potential benefits of LDH has yet to be performed in trauma patients. In those studies of LDH in trauma patients, some have shown a reduction in DVT with LDH but usually it was not significant. Sample sizes in these studies were small, and hence, a type II statistical error cannot be excluded. The results of LDH use in trauma, with regards to PE, are even more vague. We are aware of only two studies employing a combined modality of LDH and mechanical prophylaxis.

II.   Process

A Medline review from 1966 to the present, revealed several hundred articles related to the use of LDH in medical and general surgical patients. Only the 8 articles related to the use of LDH in trauma patients were utilized for the following recommendations.

III.   Recommendations

A.   Level I

LDH has little, if any, benefit as a sole agent for prophylaxis in the trauma patient at high risk for venous thromboembolism (VTE).

B.   Level II

For patients in whom bleeding could exacerbate their injuries (such as those with intracranial hemorrhage, incomplete spinal cord injuries, intraocular injuries, severe pelvic or lower extremity injuries with traumatic hemorrhage, and intra-abdominal solid organ injuries being managed nonoperatively), the safety of LDH has not been established and an individual decision should be made when considering anticoagulant prophylaxis.

C.   Level III

There may be a role for the use of LDH in combination with sequential compression devices (SCDs) in trauma patients at high risk for VTE, although there is little data in trauma patients to support such a combination.

IV.   Scientific Foundation

Heparin is a naturally occurring polysaccharide in varying molecular weight from 2,000-40,000. Low dose heparin augments the activity of antithrombin III, a potent, naturally occurring inhibitor of activated factor X (Xa) and thrombin, which produces interruption of both the intrinsic and extrinsic pathways. Low-dose heparin causes only minimal or no change in conventional clotting tests, such as the PTT.

A meta-analysis of 29 trials in over 8000 surgical patients demonstrated that LDH significantly decreased the incidence of DVT from 25.2%, in patients with no prophylaxis, to 8.7% in treated patients (p< 0.001). ¹ Similarly, PE was halved by LDH treatment; the incidence was 0.5% in treated patients compared to 1.2% in controls (p<0.001).¹ In double-blind trials, the incidence of major hemorrhage was higher in treated patients (1.8%) than controls (0.8%) but this was not significant.¹ Minor bleeding complications, such as wound hematomas, were more frequent in LDH treated patients (6.3%) compared to controls (4.1%, p<0.001).¹

Studies on the use of LDH in trauma patients are inconclusive. Shackford et al.² in a nonrandomized, uncontrolled trial of 177 high risk trauma patients compared no prophylaxis (n=25), LDH (n=18), LDH + SCD (n=53), and SCD only (n=81) according to physician preference. There was no significant difference in VTE rate in the groups receiving no prophylaxis (4%) vs. those who received prophylaxis (LDH 6%; LDH + SCD 9%; SCD 6%). In a relatively large, nonrandomized, unblinded prospective study of 395 trauma patients admitted with an ISS > 9 who received either LDH, SCD, or no prophylaxis, Dennis et al.³ demonstrated a VTE rate of 3.2%, 2.7%, and 8.8%, respectively, with a hand-held Doppler flow probe. There was no statistically significant difference in VTE rate for the two types of prophylaxis, but there was a statistically significant difference in VTE in those who received prophylaxis vs. those who didnít (p<0.02;X²). Specific analysis of those who received LDH vs. no prophylaxis revealed no significant difference in DVT rate. Ruiz et al.,⁴ in 100 consecutive trauma patients admitted to their trauma center with an ISS > 10, looked at the incidence of VTE according to type of prophylaxis received. In the 50 patients who received LDH, there was a DVT rate of 28% vs. a DVT rate of only 2%, in the 50 patients who received no prophylaxis. Closer scrutiny of this nonrandomized study revealed that the patients who received LDH were more severely injured (mean ISS 31 vs. 22) and had a longer period of immobilization (17.9 vs. 8.0 days), which certainly could have contributed to the higher DVT rate seen in the LDH prophylaxis group. Knudson et al.⁵ reported on 251 patients in a cohort study who received LDH, SCD, or no prophylaxis. They failed to show any effectiveness with prophylaxis in most trauma patients, except in the subgroup of patients with neurotrauma in which SCD was more effective than control in preventing DVT. Upchurch et al. ⁶ compared 66 ICU-dependent trauma patients who received either no VTE prophylaxis or LDH. The groups were well matched according to age, ISS, length of stay, and mortality. There was no significance in VTE rate between the two groups. In this same study, the authors performed a meta-analysis of the current literature concerning the use of LDH in trauma patients. Five studies met their entry criteria for inclusion in the meta-analysis which included 1,102 patients.^2,3,4,5 This meta-analysis demonstrated no benefit of LDH as prophylaxis compared to no prophylaxis (10% vs.7%; P=0.771). Geerts et al.⁷ randomized 344 trauma patients to receive LMWH vs. LDH and found significantly fewer DVTs with LMWH than with LDH (31% vs. 44%, p=0.014 for all DVT; and 15% vs 6%, p=0.012 for proximal DVT). This study had no control group but, compared with the predicted DVT rate if the study patients had not received prophylaxis, the risk reduction for LDH was only 19% for DVT and only 12% for proximal DVT while the comparative risk reductions for LMWH were 43% and 65%, respectively. Napolitano et al.⁸ used a serial ultrasound screening protocol for DVT in 437 patients who were given four types of prophylaxis (LDH, VCB, LDH and VCB, no prophylaxis) according to their attending surgeonís preference. There was no significant difference in DVT rate between groups (8.6%, 11.6%, 8.0%, 11.9% respectively).

VI.   Summary

The overall effectiveness of LDH for prophylaxis of VTE in trauma patients remains unclear. Most studies show no effect of LDH on VTE. Most studies on the use of LDH in trauma patients suffer from severe methodologic errors, poor study design, and small sample size, suggesting the possibility of a type II statistical error.

VII.   Future Investigation

There is enough accumulated data to warrant not using LDH in a trial in high risk trauma patients. Future studies should focus on the potential benefit of LDH in low risk trauma patients.

VI.   References

Reference Conclusions